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We herein report a case of myoclonic epilepsy with ragged-red fibers (MERRF) harboring a novel variant in mitochondrial cysteine transfer RNA (MT-TC). A 68-year-old woman presented with progressive myoclonic epilepsy with optic atrophy and peripheral neuropathy. A skin biopsy revealed p62-positive intranuclear inclusions. No mutations were found in the causative genes for diseases known to be related to intranuclear inclusions; however, a novel variant in MT-TC was found. The association between intranuclear inclusions and this newly identified MERRF-associated variant is unclear; however, the rare complication of intranuclear inclusions in a patient with typical MERRF symptoms should be noted for future studies.

Objective To investigate the temporal course of medication response and associated prognostic factors in a cohort of juvenile myoclonic epilepsy (JME) patients over a long-term follow-up. Materials and methods Data from 113 JME patients diagnosed according to recently proposed class II criteria were retrospectively reviewed. Early sustained remission was defined as 4-year seizure remission starting within 2 years from the first antiseizure medication (ASM) intake, as opposed to delayed sustained remission. Spontaneous relapse rate (ie, not related to ASM withdrawal) was also investigated, along with factors associated with seizure relapse. Results Four-year seizure remission was obtained by 76/113 (67.3%) subjects. Early sustained remission was achieved by 45/76 (59.2%) patients. Absence seizures were significantly associated with no-remission at multivariable multinomial logistic regression analysis. Catamenial seizures and earlier age at epilepsy onset significantly predicted delayed sustained remission. Spontaneous seizure relapse after 4-year remission occurred in 15.7% of patients with early sustained remission and in 35.5% of those with delayed sustained remission (p = 0.045). The most common concomitant factors for a spontaneous relapse were irregular lifestyle habits and pregnancy-related switch from valproate to another ASM. Patients with a history of catamenial seizures were more likely to experience a spontaneous generalized tonic-clonic seizure relapse after 4-year remission at univariable analysis. Significance Our data support the prognostic relevance of early medication response in JME patients. Furthermore, the prognostic significance of catamenial seizures and the impact of valproate switch on seizure relapse after a prolonged remission account for the challenging therapeutic management of women with childbearing potential.

У статті подані сучасні уявлення щодо етіології, патогенезу, клінічних проявів, підходів до діагностики й лікування рідкісної форми ідіопатичної генералізованої епілепсії — синдрому Дживонса. Також наводиться опис клінічного випадку епілептичного міоклонусу повік з абсансами (синдрому Дживонса) у підлітка.

The aim of this study was to investigate ictal vocalizations associated with myoclonic (MS) and myoclonic-atonic seizures (MAS) in patients with myoclonic epilepsy in infants (MEI) and epilepsy with myoclonic-atonic seizures (EMAS, Doose syndrome), respectively. Subjects were retrospectively recruited among patients with MEI and EMAS for whom ictal video-polygraphs were recorded between 1990 and 2019. We reviewed all MS and MAS in order to estimate how often they were associated with vocalizations, and analyze the temporal relationship between vocalizations and spike-wave complexes (SWCs) and myoclonic EMG potentials based on simultaneous examination of the polygraphs and sound signals. Ictal video-polygraphs from 15 patients with MEI (2-34 MS per patient) and 26 with EMAS (2-26 MAS per patient) were examined. Ictal vocalizations were audible in two patients with MEI (11%; 3-18 MS per patient) and nine with EMAS (35%; 2-11 MAS per patient). Sounds were always non-speech and were immediately followed by head or body dropping in the case of MAS. Detailed analysis based on simultaneous and synchronous examination of video-polygraphs and sound signals in one patient with MEI and five patients with EMAS demonstrated that the onset of the ictal vocalizations corresponded to that of the myoclonic EMG potentials and negative spike components of SWC. Comparison of the length of myoclonic EMG potentials as well as the strength of drop seizures between MAS with and without vocalizations revealed that MAS with vocalizations were associated with longer myoclonic EMG potentials and stronger drop seizures than MAS without vocalizations (p

Background Electrophysiological techniques have been used for discriminating myoclonus from other hyperkinetic movement disorders and for classifying the myoclonus subtype. This study was carried out on patients with different subtypes of myoclonus to determine the electrophysiological characteristics and the anatomical classification of myoclonus of different etiologies. This study included 20 patients with different subtypes of myoclonus compared with 30 control participants. Electrophysiological study was carried out for all patients by somatosensory evoked potential (SSEP) and electroencephalography (EEG) while the control group underwent SSEP. SSEP was evaluated in patients and control groups by stimulation of right and left median nerves. Results This study included 50 cases with myoclonus of different causes with mean age of 39.3 ± 15.7 and consisted of 23 males and 27 females. Twenty-nine (58%) of the patients were epileptics, while 21 (42%) were non-epileptics. Cases were classified anatomically into ten cases with cortical myoclonus (20%), 12 cases with subcortical myoclonus (24%), and 28 cases with cortical–subcortical myoclonus (56%). There was a significant difference regarding the presence of EEG findings in epileptic myoclonic and non-epileptic myoclonic groups (P = 0.005). Also, there were significant differences regarding P24 amplitude, N33 amplitude, P24–N33 peak-to-peak complex amplitude regarding all types of myoclonus. Primary myoclonic epilepsy (PME) demonstrated significant giant response, juvenile myoclonic epilepsy (JME) demonstrated no enhancement compared to controls, while secondary myoclonus demonstrated lower giant response compared to PME. Conclusion Somatosensory evoked potential and electroencephalography are important for the diagnosis and anatomical sub-classification of myoclonus and so may help in decision-making regarding to the subsequent management.

Epileptic syndromes are well-defined conditions comprising particular clinical features [seizure types, age of onset, response to treatment] and characteristic electroencephalographic changes, while their etiology and subsequent prognosis may vary. The recognition of these syndromes is fundamental for pediatric neurology practice, representing an essential learning topic in this field. Nevertheless, many epileptic syndromes are still quite unfamiliar to students, residents and even neurologists, because of their low incidence and their minimal representation in the literature. This narrative review discusses the concept of epileptic syndromes and revisits seven lesser-known or uncommon syndromes in order to summarize their core clinical features, which can become important clues for daily neurological practice, namely epilepsy of infancy with migrating focal seizures, myoclonic epilepsy of infancy, self-limited infantile epilepsy, myoclonic encephalopathy in nonprogressive disorders, Jeavons syndrome, and epilepsy with myoclonic absences.

Objectives Juvenile myoclonic epilepsy (JME) is the most prevalent form of generalized epilepsy in the community. Though the response to medication is good in most patients, long-term medication usage may lead to poor compliance, side effects, and other epilepsy-related social issues. The aim of this study was to describe the demography, clinical features, and therapeutic response in patients with JME who have had at least 10 years of duration of epilepsy. Materials and Methods A retrospective study of 56 patients (M:F=26:30; mean age: 14.5 ± 5.1 years) with JME attending neurological services in a tertiary care neurological center in South India with more than 10 years disease duration was performed. Results All patients had myoclonic jerks, 94% had generalized tonic–clonic seizure, and only 7.1% had features of absence seizures. Seizures were controlled in 60% of cases at the end of 10 years of epilepsy. Thirty-eight patients (67.8%) were on valproate. Control of seizures at the end of the first and fifth years of epilepsy, frequent myoclonic jerks at the onset, and treatment with valproate in the first year of disease resulted in controlled seizures at the end of 10 years. No patient was off medications at the end of 10 years of epilepsy or at the last follow-up. Conclusion About 40% of our patients continued to have seizures even 10 years after the onset of epilepsy. Regular and long-term medication may be required in JME. Early control of seizures, response to valproate, and frequent myoclonia at onset were found to confer better prognosis.

Introduction Dravet syndrome (DS) is severe myoclonic epilepsy in infancy and associated with a heterozygous mutation of the gene for the sodium channel alpha 1 subunit (SCN1A). Recently, adult patients with DS have been reported to show parkinsonism, but no corresponding neuroimaging data are available. Here, we present neuroimaging data in 2 adult patients with DS showing parkinsonian symptoms. Case report Case 1: A man who had intractable seizures from the age of 1 year and 2 months was diagnosed with DS at 7 with a mutation in the SCN1A gene. At 18, he had parkinsonian symptoms such as masked face and bradykinesia. At 20, he was admitted to our department. Dopamine transporter single-photon emission computed tomography (DAT SPECT) showed no decrease in striatal binding of 123I–N–ω–fluoropropyl–2β–carbomethoxy–3β–(4–iodophenyl) nortropane (123I-FP-CIT), and myocardial scintigraphy showed no decrease in cardiac uptake of 123I-metaiodobenzylguanidine (123I-MIBG). Levodopa showed no significant improvement in his symptoms. Case 2: A woman who had febrile seizures at 4 months of age and myoclonic seizures at 1 year and 5 months was diagnosed with DS at 31. She had myoclonus, resting tremor, hypertonia, antecollis, crouch gait, and bradykinesia. DAT SPECT imaging showed no decrease in striatal FP-CIT binding, and levodopa did not improve her symptoms. Discussion The normal DAT SPECT and 123I-MIBG results suggest that dopaminergic neurons projecting onto striatal neurons were not impaired in our patients, explaining the lack of response to levodopa. Thus, dopamine imaging can help to guide treatment decisions in patients with DS and parkinsonism.

Previously known as severe myoclonic epilepsy of infancy, Dravet syndrome is characterized by febrile or afebrile prolonged hemiconvulsive seizures or generalized status epilepticus in an infant with previously normal development. Immediate management of status epilepticus is critical in these patients. Early control of status epilepticus prevents further brain damage; however, there is no consensus regarding the management of status epilepticus in children with Dravet syndrome, as many conventional antiseizure medications that are recommended in the management of status epilepticus worsen the seizures in these patients. A 2.5-year-old girl child patient was referred due to status epilepticus which was refractory to antiseizure medications. Sodium valproate, nitrazepam, ketogenic diet, intravenous phenytoin, and midazolam continuous infusion were administered. After controlling status epilepticus, the probable diagnosis of Dravet syndrome was proposed and confirmed by a mutation in SCN1A. As previously stated in numerous case reports, phenytoin worsens seizures in patients with Dravet syndrome. Therefore, it seems logical that in every infant with status epilepticus and probable Dravet syndrome, the practicing physician considers administering intravenous valproate or even midazolam continuous infusion instead of intravenous phenytoin.

Lafora disease is a genetic disease caused, in humans, by mutations in EPM2A and NHLRC1 genes, resulting in accumulation of polyglucosan bodies within neurons. Affected subjects present progressive neurological signs characterised primarily by myoclonic epilepsy. In dogs, Lafora disease has been described mainly in miniature wire-haired Dachshunds, where a dodecamer expansion in NHLRC1 gene has been identified. The same mutation has then been detected in the Basset Hound, Beagle, Chihuahua and Pembroke Welsh Corgi breeds. This is the first case of a Newfoundland dog with myoclonic epilepsy diagnosed with Lafora disease based on confirmed dodecamer expansion in the NHLRC1 gene. Lafora disease is being progressively recognised in different unrelated breeds suggesting a wider distribution in the canine population than previously thought.

The pathology of Dravet syndrome is of particular importance in children. In this article we analyze the involvement of the SCN1A gene in Dravet syndrome, we approach the new treatment strategies in Dravet syndrome.

ZusammenfassungDie Lafora-Erkrankung ist eine autosomal-rezessiv vererbte lysosomale Speicherkrankheit, bei der es zur Akkumulation neurotoxischer Glykogenprodukte überwiegend in Zellen des zentralen Nervensystems, aber auch anderer Organe kommt. Symptome in Form einer progressiven myoklonischen Epilepsie treten typischerweise um das 7. Lebensjahr auf. Eine ursächliche Therapie ist nicht möglich, zumindest anfänglich können die Symptome mit modernen Antiepileptika vermindert werden. Im vorliegenden Fall zeigte ein ca. 7-jähriger Beagle tagesformabhängige Faszikulationen, fokale und generalisierte Myoklonien bis hin zum kurzen tonisch-klonischen Krampfanfall. Die Symptomatik ließ sich durch Stress, Geräusche und Licht auslösen und verstärken. Zur Sicherung der klinischen Diagnose einer Lafora-Erkrankung wurden Proben aus Haut-, Leber-, Muskel- und Nervengewebe entnommen. In den Muskelbioptaten gelang der Nachweis der Lafora-typischen sarkoplasmatisch PAS-positiven, scholligen Ablagerungen. In den Bioptaten der anderen Gewebe fehlten die typischen Einschlüsse. Eine anfängliche Therapie mit Phenobarbital und Imepitoin war erfolglos. Durch die Therapie mit Levetiracetam konnten die klinischen Symptome deutlich reduziert werden. Zum Zeitpunkt der Manuskripterstellung, 2 Jahre nach Diagnosestellung, wies der 9-jährige Hund gelegentliche, stressinduziert gehäufte fokale Myoklonien auf. Zu einem Kollaps mit Seitenlage oder einem tonisch-klonischen Krampfanfall kam es nicht mehr.

Neuropathies in Myoclonic Epilepsy with Ragged Red Fibers (MERRF) syndrome are frequent but ganglionopathies have never been reported. We retrospectively identified 24 patients with MERRF mutations in the neuromuscular center Nord/Est/Ile de France (Pitié-Salpêtrière, Paris, France). Seventeen nerve conduction studies (NCS) were available. Five patients had MERRF syndrome and ganglionopathy, a pure sensory neuropathy. All of them displayed ataxia and mild clinical sensory abnormalities. Ganglionopathies have been reported in mitochondrial diseases but never in MERRF syndrome. We suggest that patients presenting with ganglionopathy, especially if associated with myopathy, lipomatosis or epilepsy, should be screened for MERRF mutations.

Neuronal ceroid Lipofuscinosis (NCL), inherited disorders of lysosomal storage disorders, constitute the most common progressive encephalopathies with an incidence of 1.3 to 7 in 100,000 live births. We reported clinical, electrophysiological, radiological, ultrastructural, and molecular genetic features of NCL. This is a retrospective review, in a tertiary care center from January 2016 to December 2019. All children with clinical features of NCL and confirmed by pathogenic mutation and/or enzyme assay were included. A total of 60 children (male:female = 3:1) were studied. The commonest type was CLN 2 (41.7%). Neuroregression, seizures, and ataxia were present in all cases. Retinal arterial attenuation was seen in 38.33% cases. Magnetic resonance imaging (MRI) brain was abnormal in all patients, thalamic and caudate nucleus atrophy common in CLN1 (62%). Electroencephalography was abnormal in all children, but photoparoxysmal response at low intermittent photic stimulation frequencies was seen in four children of CLN2. Electron microscopy done in 43 children revealed abnormal inclusions in 20 (46.52%) children. Enzyme study showed low levels in 36 (78%) out of 46 cases. Of these, 21 had low tripeptidyl peptidase and 15 had low palmitoyl protein thioesterase levels. Molecular testing done in 26 cases showed pathogenic variant in 23 (88%) cases. Infantile onset with thalamic atrophy on MRI is common in CLN1 and refractory epilepsy, visual impairment and specific EEG changes are common in CLN2. These features are helpful in selecting enzyme assay for CLN1 versus CLN2. Electron microscopy helped in the diagnosis and genetic testing in subtyping. Thus, a multimode approach played a role in the diagnosis of NCL.

Refractory epilepsy is due to that drug-resistant epilepsy in which there is no improvement after the applica-tion of various antiepileptic drugs (AEDs). The Telethon Children's Rehabilitation Center cares for a large population of children with some type of epilepsy. Recently, the application of the home intervention proto-col for the ketogenic diet (DC) has increased. A few years ago, DC was only attended with extreme surveil-lance in a hospital center under rigid schemes. With this background, the objective of this study was to describe the experience and findings of a series of 10 cases of children with refractory epilepsy treated with this DC protocol over the course of at least 1 year. All the cases of children (n = 10) attended at the Telethon Children's Rehabilitation Center, Aguascalientes, Mexico, who were treated with the ketogenic diet between the dates of February 2010 and June 2015, were reviewed by means of an electronic clinical record criteria for refractory epilepsy, as well as surveillance for pediatric neurology and nutrition. The DC home interven-tion protocol was established under the criteria of Lambruschini-Nilo & Gutierrez-Sanchez, where it started with a classic type DC with a 2: 1 ratio during the first week of adaptation and then went on to the 3: 1 or 4 ratio: 1 corresponding according to patient tolerance. The reduction in the number of crises was measured at 3 months and one year after surgery. A one-way ANOVA general linear model with repeated measures was applied to measure the efficacy at 3 months and one year of treatment, finding statistical significance when comparing the results means of the number of epileptic events before the diet (p =

The mitochondrial tRNALys (mt-tRNALys) mutation is initially associated with myoclonic epilepsy and ragged-red fibers (MERRF). The clinical, laboratory, morphologic and molecular findings from 22 mt-tRNALys mutation carriers from local database in East China were analyzed retrospectively. We identified 13 symptomatic and 9 asymptomatic individuals with a known pathogenic mitochondrial tRNALys mutation. The most common mutations were m.8344 A>G (81.8%), m.8363G>A (9.1%), m.8356 T>C (4.5%) and m.8356 T>G (4.5%). The degree of mutation heteroplasmy in blood was high both in symptomatic (mean 64.5%, range 41–82%) and asymptomatic individuals (mean 53.1%, range 21–78%). Age at onset ranged from 6 year-old to the age of 66 years (mean 35.8 ± 16.4 years old). The most frequent symptoms were muscle weakness (76.9%), exercise intolerance (76.9%), elevated creatine kinase levels (61.5%), peripheral neuropathy (69.2%) and cerebellar ataxia (61.5%), while myoclonus was only present in 23.1% of symptomatic patients. A diagnosis of mitochondrial myopathy (MM) and neuropathy ataxia and retinitis pigmentosa (NARP/NARP-like) syndrome was made in 77% of symptomatic patients, whereas the classic syndrome of myoclonic epilepsy with ragged-red fibers (MERRF) was rare (23%). In this cohort of patients with mt-tRNALys mutation, more than one third of our patients did not develop signs and symptoms of central nervous system involvement even in later stages of the disease, indicating the necessity to investigate the mt-tRNALys gene in ‘pure’ mitochondrial ‘myo-neuropathy’.

The mechanisms of refractory epilepsy (RE) are most likely multifactorial, involving environmental, genetic, as well as disease- and drug-related factors. We aimed to study is to investigate the possible association of two ABCB1 gene polymorphism (C3435T and C1236T) with the development of RE in Iraqi patients. One hundred patients with either generalized tonic–clonic seizures, myoclonic epilepsy, or absence epilepsy comprised of 60 patients responsive to AEDs and 40 patients who were refractory to treatment who used multi AEDs for at least one month were studied. Fifty family-unrelated age- and sex-matched healthy subjects represent the control group. ABCB1 gene fragments corresponding to two targeted polymorphisms were amplified with conventional polymerase chain reaction using specific sets of primers. Genotyping was performed by restriction fragment length polymorphism (RFLP) technique. Epileptic patients refractory to AEDs showed a significantly higher frequency of CC genotypes of C3435T polymorphism than controls. Allele C was significantly higher in patients than controls and far more frequent among patients with RE. C1235T polymorphism had no significant role neither in the incidence of epilepsy nor in the AEDs resistance. The CT haplotype was more frequent among patients refractory to AEDs. In contrast, the haplotype block TT was more frequent among responsive (41.3%) than refractory patients (28.7%) (p = 0.068). The CC genotype and C allele of the C3435T polymorphism can increase the risk of RE. The haplotype block CT of C3435T and C1236T can predispose for epilepsy as well as the drug resistance.

Dravet syndrome (DS), previously known as severe myoclonic epilepsy of infancy, is a severe developmental and epileptic encephalopathy caused by loss-of-function mutations in one copy of SCN1A (haploinsufficiency), located on chromosome 2q24, with decreased function of Nav1.1 sodium channels in GABAergic inhibitory interneurons. Pharmacoresistant seizures in DS start in the infancy in the form of hemiclonic febrile status epilepticus. Later, other intractable seizure types develop including myoclonic seizures. Early normal development in infancy evolves into moderate to severe intellectual impairment, motor impairment, behavioral abnormalities, and later a characteristic crouching gait. Clobazam, valproate, levetiracetam, topiramate, zonisamide, ketogenic diet, and vagus nerve stimulation had been shown to be effective, but even with polytherapy, only 10% of patients get adequate seizure control. The author provides a narrative review of the current treatment paradigm as well as recent advances in the management of DS based on a comprehensive literature review (MEDLINE using PubMed and OvidSP vendors with appropriate keywords to incorporate recent evidence), personal practice, and experience. In recent years, the treatment paradigm of DS is changing with the approval of pharmaceutical-grade cannabidiol oil and stiripentol. Another novel antiepileptic drug (AED), fenfluramine, had also shown excellent efficacy in phase 3 studies of DS. However, these AEDs primarily control seizures without addressing the underlying pathogenesis and other important common comorbidities such as cognitive impairment, autistic behavior, neuropsychiatric abnormalities, and motor impairment including crouching gait. Several agents targeted for DS are in the developmental stage: TAK935, lorcaserin, clemizole, huperzine analog, ataluren, selective sodium channel modulators and activators, antisense oligonucleotide therapy, and adenoviral vector therapy. As DS is associated with a high risk of sudden unexpected death in epilepsy, seizure detection devices can be used in this population for testing and clinical validation of these devices.

DRPLA (dentatorubral–pallidoluysian atrophy) is a neurodegenerative disorder caused by cytosine-adenine-guanine (CAG) trinucleotide repeat expansion (>48) in ATN1 gene at 12p13.31 locus inherited in an autosomal-dominant manner. The key clinical manifestations of DRPLA are ataxia, dementia, and myoclonic epilepsy and have variable association with intellectual disability, behavioral changes, epileptic seizures, and choreoathetosis. It is most commonly reported in Japanese population with a prevalence of 0.2–0.7/100,000. Here we report a three-generation first Indian family identified to carry a pathogenic CAG expansion in ATN1 and clinical features conformed to its key manifestations.

Objective To characterize the visual evoked potentials (VEP) in patients with type 3 Gaucher disease (GD) with or without progressive myoclonus epilepsy. Methods Three young adults with progressive myoclonus epilepsy (type 3a GD) and two children without progressive myoclonus epilepsy (type 3b GD) were enrolled. Flash visual and somatosensory evoked potentials (F-VEP and SEP, respectively) were retrospectively reviewed in all patients under enzyme replacement therapy. Pattern reversal visual evoked potentials (PR-VEP) were recorded in the type 3a group. Result High-frequency components were provoked at early latencies on averaged F-VEP in all patients with type 3a and one patient with type 3b GD. Conversely, no activities were recorded in PR-VEP. The onset latency of the components began at 15.3–19.8 ms after flash stimulation. Four-five of the F-VEP examination the activities’ duration overrode the N75 waveforms and were prolonged toward the P100 peak latency. The F-VEP amplitude did not differ between the type 3a and type 3b groups, while the SEP amplitude was higher in the type 3a than in the type 3b group. Significance High-frequency components on F-VEP using bandpass filter at 10–200 Hz may help assess augmented excitability in the visual cortex of type 3 GD patients.

Progressive myoclonic epilepsies (PMEs) comprise a group of rare disorders of different genetic aetiologies, leading to childhood-onset myoclonus, myoclonic seizures and subsequent neurological decline. One of the genetic causes for PME, a mutation in the gene coding for Golgi SNAP receptor 2 (GOSR2), gives rise to a PME-subtype prevalent in Northern Europe and hence referred to as North Sea Progressive Myoclonic Epilepsy (NS-PME). Treatment for NS-PME, as for all PME subtypes, is symptomatic; the pathophysiology of NS-PME is currently unknown, precluding targeted therapy. Here, we investigated the pathophysiology of NS-PME. By means of chart review in combination with interviews with patients (n = 14), we found heat to be an exacerbating factor for a majority of NS-PME patients (86%). To substantiate these findings, we designed a NS-PME Drosophila melanogaster model. Downregulation of the Drosophila GOSR2-orthologue Membrin leads to heat-induced seizure-like behaviour. Specific downregulation of GOSR2/Membrin in glia but not in neuronal cells resulted in a similar phenotype, which was progressive as the flies aged and was partially responsive to treatment with sodium barbital. Our data suggest a role for GOSR2 in glia in the pathophysiology of NS-PME. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

Pediatric neurodegeneration is extremely rare and devastating to the families involved. We describe a rare case of pediatric neurodegeneration in a child with N-glycanase 1 (NGLY1) deficiency. This child had an autosomal recessive mutation in NGLY1, the gene coding for the enzyme NGLY1 that was found with exome sequencing. NGLY1 catalyzes protein deglycosylation by cleaving the -aspartyl glycosylamine bond of N-linked glycoproteins and is thereby a component of the endoplasmic reticulum-associated degradation pathway. This child passed away at five years of age after a prolonged clinical course with myoclonic epilepsy, choreoathetosis-like movements, lacrimal duct problems, and severe developmental delay. This autopsy case report shows images of the neuronal inclusions and liver steatosis found in this patient with NGLY1 deficiency and offers a detailed clinical history.

The association of spinal muscular atrophy (SMA) with progressive myoclonic epilepsy, also known as “SMA plus,” is a unique syndrome linked to non-survival motor neuron (non-SMN) genes. The disease starts in childhood with progressive weakness and atrophy of muscles; myoclonic epilepsy develops during later childhood, after the onset of motor symptoms. In this report, we describe a case of SMN gene unrelated SMA and myoclonic epilepsy, supported by electrophysiological and neuropathological evidences.

The high pace of gene discovery has resulted in thrilling advances in the field of epilepsy genetics. Clinical testing with comprehensive gene panels, exomes, or genomes are now increasingly available and have led to a significant higher diagnostic yield in early-onset epilepsies and enabled precision medicine approaches. These have been instrumental in providing insights into the pathophysiology of both early-onset benign and self-limited syndromes and devastating developmental and epileptic encephalopathies (DEEs). Genetic heterogeneity is seen in many epilepsy syndromes such as West syndrome and epilepsy of infancy with migrating focal seizures (EIMFS), indicating that two or more genetic loci produce the same or similar phenotypes. At the same time, some genes such as SCN2A can be associated with a wide range of epilepsy syndromes ranging from self-limited familial neonatal epilepsy at the mild end to Ohtahara syndrome, EIFMS, West syndrome, Lennox–Gastaut syndrome, or unclassifiable DEEs at the severe end of the spectrum. The aim of this study was to review the clinical and genetic heterogeneity associated with epilepsy syndromes starting in the first year of life including: Self-limited familial neonatal, neonatal-infantile or infantile epilepsies, genetic epilepsy with febrile seizures plus spectrum, myoclonic epilepsy in infancy, Ohtahara syndrome, early myoclonic encephalopathy, West syndrome, Dravet syndrome, EIMFS, and unclassifiable DEEs. We also elaborate on the advantages and pitfalls of genetic testing in such conditions. Finally, we describe how a genetic diagnosis can potentially enable precision therapy in monogenic epilepsies and emphasize that early genetic testing is a cornerstone for such therapeutic strategies.

Background Many studies of epilepsy in veterinary medicine use subjective data (eg, caregiver-derived histories) to determine seizure frequency. Conversely, in people, objective data from electroencephalography (EEG) are mainly used to diagnose epilepsy, measure seizure frequency and evaluate efficacy of antiseizure drugs. These EEG data minimize the possibility of the underreporting of seizures, a known phenomenon in human epileptology. Objective To evaluate the correlation between reported seizure frequency and EEG frequency of ictal paroxysmal discharges (PDs) and to determine whether seizure underreporting phenomenon exists in veterinary epileptology. Animals Thirty-three ambulatory video-EEG recordings in dogs showing >= 1 ictal PD, excluding dogs with status epilepticus. Methods Retrospective observational study. Ictal PDs were counted manually over the entire recording to obtain the frequency of EEG seizures. Caregiver-reported seizure frequency from the medical record was categorized into weekly, daily, hourly, and per minute seizure groupings. The Spearman rank test was used for correlation analysis. Results The coefficient value (r(s)) comparing reported seizure to EEG-confirmed ictal PD frequencies was 0.39 (95% confidence interval [CI] = 0.048-0.64, P = .03). Other r(s) values comparing history against various seizure types were: 0.36 for motor seizures and 0.37 for nonmotor (absence) seizures. Conclusions and Clinical Importance A weak correlation was found between the frequency of reported seizures from caregivers (subjective data) and ictal PDs on EEG (objective data). Subjective data may not be reliable enough to determine true seizure frequency given the discrepancy with EEG-confirmed seizure frequency. Confirmation of the seizure underreporting phenomenon in dogs by prospective study should be carried out.

BackgroundLafora disease (LD) is a fatal childhood-onset dementia characterized by the extensive accumulation of glycogen aggregates—the so-called Lafora Bodies (LBs)—in several organs. The accumulation of LBs in the brain underlies the neurological phenotype of the disease. LBs are composed of abnormal glycogen and various associated proteins, including p62, an autophagy adaptor that participates in the aggregation and clearance of misfolded proteins.MethodsTo study the role of p62 in the formation of LBs and its participation in the pathology of LD, we generated a mouse model of the disease (malinKO) lacking p62.ResultsDeletion of p62 prevented LB accumulation in skeletal muscle and cardiac tissue. In the brain, the absence of p62 altered LB morphology and increased susceptibility to epilepsy.ConclusionsThese results demonstrate that p62 participates in the formation of LBs and suggest that the sequestration of abnormal glycogen into LBs is a protective mechanism through which to reduce the deleterious consequences of its accumulation in the brain.

Celiac disease (CD) is an immune-mediated disease with varied intestinal and extraintestinal manifestations. Among extraintestinal manifestations, neurological conditions are being reported with increased frequency nowadays. We report a child of CD with progressively increasing dementia, poor scholastic performance, and myoclonic epilepsy. On further investigation, the cause of neurological manifestations was diagnosed as subacute sclerosing panencephalitis (SSPE). It is a slowly progressive neurodegenerative disorder caused by defective measles virus which is eventually fatal. The coexistence of CD and SSPE could not be found in literature.

BackgroundAmbroxol (ABX) has been suggested as an augmentative pharmacological agent for neuronopathic Gaucher disease (nGD). This study assessed the long-term safety and efficacy of combined therapy with high-dose ABX and enzyme replacement therapy (ERT) in nGD.MethodsABX+ERT therapy was administered for 4.5 years in four patients with nGD. ABX was initiated at a dose of 1.5 mg/kg/day, and the dose was escalated up to 27 mg/kg/day. The target plasma level was 10 µmol/L or less. The changes in glucocerebrosidase activity, biochemical, safety and neurocognitive findings were assessed.ResultsEnhanced residual GCcase activity was observed in all patients, as evidenced in both in vitro and in vivo studies. During the first 2 years of study with ABX (up to 21 mg/kg/day), mean seizure frequencies and neurocognitive function worsened. After ABX dosage was increased up to 27 mg/kg/day of ABX, its trough plasma concentration was 3.2–8.8 µmol/L. Drug-to-drug interaction, especially with antiepileptic drug significantly affected the pharmacokinetic parameters of ABX. Importantly, at 27 mg/kg/day of ABX, the seizure frequencies markedly decreased from the baseline, and the neurocognitive function was improved. In addition, Lyso-Gb1, a biomarker for the severity and progression of GD, was normalised in all patients. High-dose ABX was well-tolerated with no severe adverse events.ConclusionsLong-term treatment with high-dose ABX+ERT was safe and might help to arrest the progression of the neurological manifestations in GD.

Epilepsy is a common neurological disorder and identification of its causes is important for a better understanding of its pathogenesis. We previously studied a Thai family with a type of epilepsy, benign adult familial myoclonic epilepsy type 4 (BAFME4), and localized its gene to chromosome 3q26.32-q28. Here, we used single-molecule real-time sequencing and found expansions of TTTTA and insertions of TTTCA repeats in intron 1 of YEATS2 in one affected member of the family. Of all the available members in the family-comprising 13 affected and eight unaffected-repeat-primed PCR and long-range PCR revealed the co-segregation of the TTTCA repeat insertions with the TTTTA repeat expansions and the disease status. For 1116 Thai control subjects, none were found to harbour the TTTCA repeats while four had the TTTTA repeat expansions. Therefore, our findings suggest that BAFME4 is caused by the insertions of the intronic TTTCA repeats in YEATS2. Interestingly, all four types of BAFMEs for which underlying genes have been found (BAFMEs 1, 4, 6 and 7) are caused by the same molecular pathology, suggesting that the insertions of non-coding TTTCA repeats are involved in their pathogenesis.

Dravet's syndrome (DS) or severe myoclonic epilepsy of infancy is a rare, genetic, and infantile-onset epileptic encephalopathy. DS presents with recurrent febrile seizures and/or febrile status epilepticus in developmentally normal infants, and subsequently evolves into a drug-resistant mixed-seizure disorder with developmental arrest or regression. As many defining clinical features of DS do not become evident until 3 to 4 years of age, diagnosis is often delayed. Early seizure control, particularly the prevention of status epilepticus in infancy, has been shown to correlate with better long-term outcomes. Thus, early diagnosis and seizure control is crucial. Several treatment algorithms have been published in recent years to guide antiepileptic drug selection and escalation. Last year, two agents, stiripentol and cannabidiol, were approved by the U.S. Food and Drug Administration specifically for use in DS, and a third has been submitted (fenfluramine). Additional therapies, including serotonin modulators lorcaserin and trazodone, verapamil, and several first-in-class medications, are currently in various phases of investigation.

Gaucher disease is an autosomal recessive lysosomal storage disorder caused by mutations in the gene GBA1, which encodes the lysosomal protein glucocerebrosidase. Patients with Gaucher disease generally have a variety of clinical manifestations ranging from visceral to neurological involvement and some develop ocular involvement. The most commonly affected organs include the spleen, liver, and bone. Moreover, patients often have hepatosplenomegaly, thrombocytopenia, anemia, and bone involvement related to deficient glucocerebrosidase and the subsequent accumulation of glucosylceramide and glucosylsphingosine in cells. A subset of patients develops neurological manifestations, including seizures, myoclonic epilepsy, and progressive neurodegeneration. Eye involvement tends to be less common and presents with diverse clinical findings. These rare and variable ocular manifestations, involving the vitreous, retina, cornea, uvea, conjunctiva and eye movements, can pose a diagnostic challenge for clinicians, especially those not familiar with the disorder. In this review, we explore the different ophthalmologic findings reported in patients with Gaucher disease, aiming to facilitate diagnosis and expedite treatment for patients presenting with ocular manifestations of this rare disorder.

Introduction Juvenile myoclonic epilepsy (JME), also known as Janz syndrome, is a common form of generalized epilepsy of presumed genetic origin representing up to 10% of all epilepsy cases. Despite adequate anti-seizure medication (ASM) treatment, seizures persist in one-third of JME patients. Areas covered A literature search was conducted using Pubmed search on the topics of drug-resistant JME. Expert opinion About 30% of JME patients are drug-resistant. Valproate (VPA) is considered the first-choice drug. In women of childbearing potential, levetiracetam (LEV) should represent the first-choice treatment. Alternative monotherapy or add-on therapy should be considered in subjects with resistant seizures after the exclusion of pseudo-drug resistance. The choice of the add-on ASM depends on the predominant seizure type. In subjects with persistent bilateral tonic-clonic seizures, LEV or lamotrigine should be firstly considered. In patients with difficult-to-treat myoclonic seizures, clonazepam or LEV are recommended. In case of persistent absences, ethosuximide should be considered. With appropriate selection and safeguards in place, VPA should remain available as an option in women of childbearing potential whose seizures are resistant to other treatments.

Eyelid myoclonia with absences (EMA) shares some clinical characteristics with juvenile myoclonic epilepsy (JME), in which impulsivity traits have been described. Aim of the study was to evaluate whether EMA patients could present a peculiar behavioural profile.Patients with EMA, JME and healthy controls (HCs) were enrolled. Subjects with intellectual quotient80 were excluded from the study. All the enrolled subjects underwent the Italian version of the Barratt Impulsiveness Scale (BIS-11) and the three dimensions of impulsivity (motor, attentional-cognitive and nonplanning impulsivity) were considered.Seventeen patients with EMA (12 females [70.6%], age 30.8±10 years), 29 patients with JME (17 females [58.6%], age 29.1±9.7 years) and 31 HCs (15 females [48.4%], age 27.6±5.8 years) were enrolled. Both EMA and JME patients presented a borderline significantly higher BIS total score than HCs (p=0.064). EMA patients presented a significantly higher BIS nonplanning subscore than JME patients and HCs (p=0.001).The study showed the presence of peculiar behavioral characteristics in EMA patients, slightly different from patients with JME.

Objective To describe the clinical and molecular features of a group of Argentinian pediatric patients with mitochondrial DNA (mtDNA) disorders, and to evaluate the results of the implementation of a classical approach for the molecular diagnosis of mitochondrial diseases. Methods Clinical data from 27 patients with confirmed mtDNA pathogenic variants were obtained from a database of 89 patients with suspected mitochondrial disease, registered from 2014 to 2020. Clinical data, biochemical analysis, neuroimaging findings, muscle biopsy and molecular studies were analyzed. Results Patients were 18 females and 9 males, with ages at onset ranging from 1 week to 14 years (median = 4 years). The clinical phenotypes were: mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome (n = 11), Leigh syndrome (n = 5), Kearns-Sayre syndrome (n = 3), Chronic Progressive External Ophthalmoplegia (n = 2), Leber hereditary optic neuropathy (n = 2), myoclonic epilepsy associated with ragged-red fibers (n = 1) and reversible infantile myopathy with cytochrome-C oxidase deficiency (n = 3). Most of the patients harbored pathogenic single nucleotide variants, mainly involving mt-tRNA genes, such as MT-TL1, MT-TE and MT-TK. Other point variants were found in complex I subunits, like MT-ND6, MT-ND4, MT-ND5; or in MT-ATP6. The m.13513G > A variant in MT-ND5 and the m.9185 T > C variant in MT-ATP6 were apparently de novo. The rest of the patients presented large scale-rearrangements, either the “common” deletion or a larger deletion. Conclusions This study highlights the clinical and genetic heterogeneity of pediatric mtDNA disorders. All the cases presented with classical phenotypes, being MELAS the most frequent. Applying classical molecular methods, it was possible to achieve a genetic diagnosis in 30% of the cases, suggesting that this is an effective first approach, especially for those centers from low-middle income countries, leaving NGS studies for those patients with inconclusive results.

To elucidate the morphological characteristics of spike-wave complexes (SWCs) causing myoclonic seizures (MS) in childhood-onset idiopathic myoclonic epilepsies.The subjects were 8 patients, including 4 with epilepsy with myoclonic-atonic seizures (EMAS), 3 with myoclonic epilepsy in infancy (MEI) and 1 with idiopathic unclassifiable myoclonic epilepsy. Morphometric parameters of the SWCs were compared between those with MS [SWC-MS (+)] and those without MS [SWC-MS (-)], and a correlation coefficient analysis was performed between the SWC parameters and the duration of myoclonic electromyogram (EMG) potentials.A total of 155 SWC-MS (+) (range: 7 ∼ 34) and 80 SWC-MS (-) (10 each as a control) were analyzed. Comparison of the parameters of the SWCs between SWC-MS (+) and SWC-MS (-) demonstrated that the depth and the width of the positive-sharp-components (PSC) in the SWC-MS (+) were significantly deeper in amplitude and longer in duration than those in the SWC-MS (-), respectively, in all 8 patients (P 0.05), whereas the number of the polyphasic-multiple-spike-components (PMSC) and the height of negative-spike-components (NSC) were not significantly different in most of the patients, respectively. The depth and the width of PSC were also significantly correlated with the duration of myoclonic EMG potentials in all patients except one [depth of PSC (n = 7): r = 0.623 ∼ 0.888; width of PSC (n = 8): r = 0.676 ∼ 0.948, P 0.05].This study revealed that the depth and width of PSC of the SWC are positively correlated with the MS intensity in childhood-onset idiopathic myoclonic epilepsies and are an important neurophysiological marker to generate MS.

Objective: Dravet syndrome (DS) is a severe myoclonic epilepsy affecting infants and is classified among epileptic syndromes. Generally, the first seizures begin with febrile diseases during infancy. Cognitive functions and behavior of patients begin to decline from the age of two. In DS, the most common SCN1A mutation is detected. Material and Method: The study included 18 patients with DS who were presented to Inonu University Pediatric Neurology Clinic between 2012 and 2017. We retrospectively evaluated the demographic characteristics, seizure frequency, AED therapies and response to treatment. Results: The mean age of our patients was 4.22±2.12 years. The F/M ratio was 1.57. The age of onset of seizures was 6.7±2.9 months. 77% of damage affecting patients was febrile onset. 77.7% of our patients were from VPA; 66.6% of the patients benefited from BZD, and sodium voltage-gated channel alpha subunit 1 (SCN1A) mutation was detected in all of our patients. Two patients were monozygous twins and three siblings were also monozygous. The same mutation was observed in our sister patients who were monozygous and their age at seizure onset, seizure type, clinical course, and responses to AEDs were similar. The same mutation was observed in three siblings, but the age at the time of seizure, the onset of seizures, the seizure type, clinical course, and response to AEDs were different from each other. Conclusion: If neuromotor developmental retardation is associated with recurrent febrile seizures, DS should be considered among the preliminary diagnoses. Instead of this sentence, the most common cause of Dravet syndrome among these patients is the SCN1A mutation.

Photosensitivity is defined as a “photoparoxysmal response” (PPR) to intermittent photic stimulation (IPS) during an electroencephalogram (EEG). The PPR consists of spikes, spike-waves, or intermittent slow waves, ranging from localised occipital spikes (Grade 1) to generalised spike and wave or polyspike and wave complexes (Grade 4). Photosensitivity alone does not represent an epileptic syndrome, as it can be present in many categories of epileptic disorders and in 4% of healthy children or adolescents. In addition, several general factors such as sleep deprivation, alcohol abuse, and drug withdrawal should be taken into account when assessing photosensitivity as they may influence the likelihood of observing photoparoxysmal EEG results. Although photosensitivity can be considered a trait occurring across various conditions, syndromes in which all, or almost all, seizures are induced by photic stimuli can be considered syndromes of reflex epilepsy. In pure photosensitive epilepsy, seizures exclusively occur in response to photic stimulation as opposed to epilepsy with photosensitivity, where seizures may be spontaneous or elicited by photic stimulation. Pure photosensitive epilepsies include idiopathic photosensitive occipital lobe epilepsy and photosensitive benign myoclonic epilepsy of infancy. Photosensitivity is also frequently observed in juvenile myoclonic epilepsy and epilepsy with GTCS on awakening and in other severe syndromes, especially when myoclonus is also present, such as Dravet syndrome and progressive myoclonus epilepsies.

Myoclonic epilepsy presenting in a cognitively normal adolescent is often related to juvenile myoclonic epilepsy. However, there are similar clinical features that suggest progressive myoclonus epilepsy. These include cognitive or motor regression, progressively worsening seizures, persistent slowing of the background on EEG, as well as family history of epilepsy. Due to variable phenotypes, any family history of epilepsy can be significant. There are multiple causes of progressive myoclonus epilepsy. If there is a possibility of a progressive myoclonus epilepsy, it is essential to exclude mitochondrial disorders as an etiology because valproic acid, often used to treat myoclonic seizures, will worsen underlying mitochondrial disease and precipitate or worsen hepatic failure. There are no specific treatments for progressive myoclonus epilepsy, and management is symptomatic. However, it is important to make the diagnosis in order to allow the family to understand the inheritance pattern, progressive nature, and variable phenotypes of the disease.

The interesting case about a patients with myoclonic epilepsy with ragged-red fibers (MERRF) syndrome due to the variant m.8344A>G with a heteroplasmy rate of 95% reported by Felczak et al. expands the phenotypic spectrum of MERRF syndrome. The authors reported a pituitary adenoma, calcium deposits in arterial walls, and an intra-cerebral lipoma in the corpus callosum in their patient. Shortcomings of the study are that the diagnostic criteria for MERRF were not accomplished, that the patient should be rather diagnosed as a mitochondrial, multiorgan disorder syndrome (MIMODS), that no pedigree and heteroplasmy rates in first degree relative were provided, that hormone levels were not provided despite obvious endocrinological involvement, and that no serum or cerebrospinal fluid (CSF) lactate levels were reported.

This case report describes 2 siblings with myoclonic epilepsy who had novel mutations in the glutamine synthetase ( GLUL) gene: c.316C>T, p.(Arg106*) and c.42G>C, p.(Lys14Asn). Valproic acid improved seizure control, but was associated with hyperammonemic encephalopathy. Addition of carglumic acid reduced ammonia levels but drug coverage was declined. We therefore designed a protocol to measure the reduction in plasma ammonia in response to carglumic acid therapy. After the first dose of carglumic acid, Patient 1 showed a reduction in plasma ammonia levels within 3 hours, from 114 umol/L to 68 umol/L (reference 12-47 umol/L), and Patient 2 from 108 umol/L to 80 umol/L, which was sustained over a 2 week period. Overall, there was a strong negative correlation between plasma ammonia levels and carglumic acid levels (r = −0.86, p = 0.0013), and recurrence of hyperammonemic encephalopathy was not observed while the patients were taking carglumic acid.

Purpose Long-term outcomes associated with vagus nerve stimulation (VNS) therapy for progressive myoclonic epilepsy (PME) have not been studied. The purpose of this study was to report long-term outcomes of VNS therapy in two patients with PME. Methods We performed VNS therapy for two patients with PME. We reviewed the conditions of epileptic seizures, status epilepticus (SE), myoclonus, and Karnofsky performance state (KPS) scale scores at baseline and after 10 years. Results A 16-year-old boy with myoclonic epilepsy with ragged-red fibers (MERRF) underwent VNS therapy. Baseline KPS scale score was 50, seizure frequency was weekly, and SE occurred yearly. At 23 years old, KPS scale score was 10. He had remained SE-free and frequency of epileptic seizures had markedly reduced. At 24 years old, he died due to pneumonia. A woman with Gaucher's disease type III underwent VNS therapy at 20 years old. Baseline KPS scale score was 80, seizure frequency was daily, and SE occurred monthly. At 30 years old, KPS scale was 30. She remained SE-free, but still experienced epileptic seizures yearly. Both patients became lethargic during VNS-off periods, with symptoms improving to baseline levels when VNS was resumed. Conclusion Long-term outcomes with VNS showed good epileptic seizure control and freedom from SE. VNS might help maintain level of consciousness., Behavioral neuroscience; Cognitive neuroscience; Neuroscience; Neurology; Neurosurgery; Rehabilitation; Pediatrics; Vagus nerve stimulation (VNS); Long-term outcome; Progressive myoclonic epilepsy (PME); Epileptic seizure control; Consciousness.

Background Progressive myoclonic epilepsy (PME) is a group of neurodegenerative diseases with genetic heterogeneity and phenotypic similarities, and many cases remain unknown of the genetic causes. This study is aim to summarize the clinical features and study the genetic causes of PME patients. Methods Sanger sequencing of the target gene, Next Generation Sequencing (NGS) panels of epilepsy, trio-based Whole Exome Sequencing (WES) and detection of cytosine-adenine-guanine (CAG) repeat number were used to investigate the genetic causes of PME patients. Results Thirty-eight children with PME whose seizure onset age ranged from 3 months to 12 years were collected from February 2012 to November 2019 in three hospitals in Beijing, China. The seizure types included myoclonic seizures (n = 38), focal seizures (n = 19), generalized tonic-clonie seizure (GTCS) (n = 13), absence seizures (n = 4), atonic seizures (n = 3), epileptic spasms (n = 2) and tonic seizures (n = 1). Twenty-seven cases were sporadic and 11 had family members affected. Established PME-related genes were identified in 30 out of 38 (78.9%) patients who had either recessively inherited or de novo heterozygous mutations. Among these 30 cases, there were 12 cases (31.6%) of neuronal ceroid lipofuscinoses (the causing gene contains TPP1, PPT1, CLN5, CLN6 and MFSD8), two cases of sialidosis (the causing gene is NEU1), two cases of neuronopathic Gaucher disease (the causing gene is GBA), one case of spinal muscular atrophy-progressive myoclonic epilepsy (the causing gene is ASAH1), four cases of KCNC1 mutation-related PME, four cases of KCTD7 mutation-related PME, two cases of TBC1D24 mutation-related PME, one case of GOSR2 related PME, and two of dentatorubral-pallidoluysian atrophy (the causing gene is ATN1). In total, 13 PME genes were identified in our cohort. The etiology was not clear in eight patients. Conclusion PME is a group of clinically and genetically heterogeneous diseases. Genetic diagnosis was clear in 78.9% of PME patients. Various of genetic testing methods could increase the rate of genetic diagnosis. Neuronal ceroid lipofuscinoses (NCL) is the most common etiology of PME in children. Nearly one third PME children were diagnosed with NCL. GOSR2 related PME was in our cohort in Asia for the first time.

Myoclonic epilepsy in the form of status epilepticus is an extremely rare reported presentation. Herein, we describe an 87-year old male patient presenting with abrupt-onset rhythmic myoclonic jerks that were evaluated as synchronous positive and negative myoclonus. Further etiological investigations revealed that the myoclonus was associated with ictogenesis, and appropriate antiepileptic treatment provided total cessation of the movements. To my knowledge, this is a unique case of myoclonic status epilepticus in an elderly patient, which may have been associated with a cerebrovascular disease. In the presentation of this case, we will review the related literature and discuss some considerations to explain the pathophysiology of epileptic myoclonic movements and the possible role of pontine lesions.

A 17-year-old girl presented with subacute decline in ambulation, ataxia, generalized weakness, dysphagia, and asymmetric hearing loss. MRI findings include abnormal signal in medial thalami, mesencephalon, posterior pons, and medulla oblongata (figure). Magnetic resonance spectroscopy showed elevated lactate and decrease in N -acetylaspartate (figure, F). DNA isolated from muscle biopsy showed A8344G mutation of mitochondrial DNA (tRNA [Lys] gene), associated with 80% of patients with myoclonic epilepsy with ragged-red fibers (MERRF). MERRF is a rare mitochondrial disorder with variable onset and clinical presentation. Neuroradiologic findings of MERRF are reported rarely, with brainstem and cerebellar degeneration being the main feature of MERRF.1

ObjectiveTo describe the prevalence and characteristics of sleep-disordered breathing (SDB) in a large cohort of patients with genetically confirmed mitochondrial diseases.MethodsThis is a prospective observational study performed at the Neurophysiopatology Unit of Fondazione Policlinico Universitario A. Gemelli IRCCS. All participants had a defined mitochondrial disease and were investigated by full-night polysomnography.ResultsOne hundred three consecutive patients were enrolled. SDB was demonstrated in 49 patients (47.6%). Regarding phenotypes, we found differences in distribution between the groups: patients affected by progressive external ophthalmoplegia with single or multiple mtDNA deletions frequently had obstructive apneas (50% and 43.8%) or REM-related hypoventilation when associated with m.3243A>G mutations (75%). Furthermore, a high percentage of participants with maternally inherited diabetes and deafness and myoclonic epilepsy with ragged-red fibers syndromes were characterized by obstructive sleep apnea and REM-related hypoventilation, respectively. In contrast to what has been described in previous studies, central sleep apnea was rarely reported in our cohort.ConclusionsSDB has a higher prevalence in mitochondrial diseases compared to general population–based data. Overall, these results suggest that patients characterized by a specific phenotype-genotype combination are most at risk of developing a specific subgroup of SDB. The early identification of this disorder is crucial in the management of these fragile patients.

Background22q11.2 deletion syndrome (22q11.2DS) is considered as the genetic model of schizophrenia. However, its polymorphic nature has led researchers to further investigate its neuropsychiatric manifestations.MethodsWe enrolled 56 adults (38 men, 18 women) diagnosed with 22q11.2DS. All subjects were evaluated by a multidisciplinary team. The neuropsychiatric features were investigated by means of clinical and neurophysiological evaluation (video-EEG).ResultsThirty per cent of our patients were left-handed. Fifty-eight per cent had a low IQ, and 22 of 56 subjects had psychotic disorders (13 of 22 with schizophrenia). Eighteen patients reported at least one seizure in their lifetime, and ten were diagnosed with epilepsy; among them, seven had genetic generalised epilepsy (GGE), and five of seven showed features suggestive of juvenile myoclonic epilepsy (JME). Video-EEG recordings revealed generalised epileptiform abnormalities in 24 of 56 cases. Besides, only one patient with epilepsy had a cardiac malformation. Lastly, 31 of 56 subjects presented with parkinsonism, 16 of whom were taking neuroleptics. None of the 15 patients with parkinsonism not related to neuroleptic therapy was diagnosed with epilepsy, compared with 6 of those taking antipsychotics.Conclusions22q11.2DS is characterised by left-handedness and neuropsychiatric features such as cognitive impairment, schizophrenia, epilepsy and parkinsonism. GGE, mostly the JME phenotype, is the predominant epilepsy type. The significant association between 22q11.2DS and parkinsonian features confirms these patients’ genetic susceptibility to parkinsonism. Despite the lack of any conclusive evidence, our study suggests a possible relationship between the analysed clinical variables: (1) an inverse correlation between low IQ/psychosis/epilepsy and major cardiac diseases; (2) a direct association between psychosis and both mental delay and epilepsy; and (3) an inverse correlation between parkinsonism and epilepsy.

Background MERRF (Myoclonic Epilepsy with Ragged Red Fibers) is a rare multisystem clinical disorder due to a pathogenic variant of the mitochondrial DNA. Rare symptoms of MERRF include multiple systemic lipomatosis with symmetric uncapsulated lipomas occurs generally on the posterior cervical region and upper back. Methods We report the clinical case of a 46 years-old Caucasian man with MERRF syndrome who presented with MSL on the right cervical region. We decided to perform a mini-invasive approach using laparoscopic instruments. We performed a 10-mm incision about 5 cm under the mass and conducted a blunt dissection of the subcutaneous plane. Then we positioned a 10-mm port and started CO2 insufflation until 10 mmHg to expand the subcutaneous space. During the procedure we setted insuflation to 8 mmHg with the aim to avoid massive subcutaneous emphysema and compression on vascular structures and trachea. We identified the avascular plane between muscular fascia and giant lipoma to perform a blunt sharp dissection. During dissection we identified clear landmarks like pectoralis fascia and sternocleidomastoid muscle. At the end of dissection we morcellated the benign lipomatous lesion for extraction through 10-mm port side. Discussion Video-assisted surgical techniques offer an effective and cosmetically superior approach for excising benign subcutaneous masses. Endoscopic technique has already been adopted in other surgical specialties like pediatric surgery. Conclusion In this case we used laparoscopic standard instruments with CO2 insuflation in order to create a avascular dissection plane and reduce post-operative wound and nerve complications.